Allocation of gene products to daughter cells is determined by the age of the mother in single Escherichia coli cells.

Gene expression and growth rate are highly stochastic in Escherichia coli. Some of the growth rate variations result from the deterministic and asymmetric partitioning of damage by the mother to its daughters. One daughter, denoted the old daughter, receives more damage, grows more slowly and ages. To determine if expressed gene products are also allocated asymmetrically, we compared the levels of expressed green fluorescence protein in growing daughters descending from the same mother. Our results show that old daughters were less fluorescent than new daughters. Moreover, old mothers, which were born as old daughters, produced daughters that were more asymmetric when compared to new mothers. Thus, variation in gene products in a clonal E. coli population also has a deterministic component. Because fluorescence levels and growth rates were positively correlated, the aging of old daughters appears to result from both the presence of both more damage and fewer expressed gene products.

Early detection of high disease activity in juvenile idiopathic arthritis by sequential monitoring of patients' health-related quality of life scores.

Juvenile idiopathic arthritis (JIA) is a chronic disease. During its "high disease activity (HDA)" stage, JIA can cause severe pain, and thus could seriously affect patients' physical and psychological health. Early detection of the HDA stage of JIA can reduce the damage of the disease by treating it at an early stage and alleviating the painful experience of the patients. So far, no effective cure of JIA has been found, and one major goal of disease management is to improve patients' quality of life. To this end, patients' health-related quality of life (HRQOL) scores are routinely collected over time from JIA patients. In this paper, we demonstrate that a new statistical methodology called dynamic screening system (DySS) is effective for early detection of the HDA stage of JIA. By this approach, a patient's HRQOL scores are monitored sequentially, and a signal is given by DySS once the longitudinal pattern of the scores is found to be significantly different from the pattern of patients with low disease activity. Dimension reduction of the observed HRQOL scores and the corresponding impact on the performance of DySS are also discussed.

Cell aging preserves cellular immortality in the presence of lethal levels of damage.

Cellular aging, a progressive functional decline driven by damage accumulation, often culminates in the mortality of a cell lineage. Certain lineages, however, are able to sustain long-lasting immortality, as prominently exemplified by stem cells. Here, we show that Escherichia coli cell lineages exhibit comparable patterns of mortality and immortality. Through single-cell microscopy and microfluidic techniques, we find that these patterns are explained by the dynamics of damage accumulation and asymmetric partitioning between daughter cells. At low damage accumulation rates, both aging and rejuvenating lineages retain immortality by reaching their respective states of physiological equilibrium. We show that both asymmetry and equilibrium are present in repair mutants lacking certain repair chaperones, suggesting that intact repair capacity is not essential for immortal proliferation. We show that this growth equilibrium, however, is displaced by extrinsic damage in a dosage-dependent response. Moreover, we demonstrate that aging lineages become mortal when damage accumulation rates surpass a threshold, whereas rejuvenating lineages within the same population remain immortal. Thus, the processes of damage accumulation and partitioning through asymmetric cell division are essential in the determination of proliferative mortality and immortality in bacterial populations. This study provides further evidence for the characterization of cellular aging as a general process, affecting prokaryotes and eukaryotes alike and according to similar evolutionary constraints.

Development and validation of the QUT corneal nerve grading scale.

PURPOSE: The aim of this study was to develop and validate a grading scale to facilitate the estimation of the amount of nerve tissue in images of the corneal subbasal nerve plexus captured using in vivo laser scanning corneal confocal microscopy (LSCCM). METHODS: Images of the corneal subbasal nerve plexus obtained using a Heidelberg LSCCM were sourced from a large image bank at the Queensland University of Technology (QUT). These images were used to construct a grading scale for depicting the amount of nerve tissue, ranging from 0 (sparse) to 4 (extensive). Twenty-five observers graded 20 images of a known corneal nerve fiber length (defined as the total length of nerves per unit area) on 2 occasions, at least 2 weeks apart. An equivalent calculated grade was determined for each test image from known values of corneal nerve fiber length. RESULTS: The intraclass correlation coefficient for repeat gradings was 0.88 (P < 0.001). Intraobserver and interobserver repeatabilities were unrelated to the calculated grade (P = 0.467 and P = 0.530, respectively). Grading can be performed with average 95% confidence limits of ±1.2 grading units. Overall grading estimates did not differ between observers (P = 0.998). There was a strong agreement between the estimated and calculated grades (intraclass correlation coefficient = 0.92, P < 0.001). CONCLUSIONS: We have developed the QUT Corneal Nerve Grading Scale, which is demonstrated to be repeatable, reliable, precise, and accurate. This tool provides clinicians and researchers with a simple and convenient pictorial reference for assessing, comparing, and monitoring the corneal subbasal nerve plexus with reference to LSCCM images.